Editorial: Chronic autoimmune arthritis, infections and vaccines

The link between autoimmunity and infection continues to represent an intriguing immunologic conundrum for scientist and a frequent clinical challenge for patients and physicians. Patients with chronic autoimmune arthritis indeed have an increased risk of infections, mainly due to the dysregulation of their immune system and the use of immunosuppressive therapy. Infections in these patients are more frequent, have a more severe clinical course, eventually with prolonged viral persistence, compared to the general population and represent a frequent cause of death. Besides, infections can trigger autoimmune diseases via different immunologic mechanisms such as molecular mimicry, epitope spreading, by-stander activation and can also induce disease relapses. SARS-CoV-2 infection represents a dramatic example of this complex connection. It is known, indeed, that different autoimmune manifestations can complicate SARS-CoV-2 infection such as uncontrolled host-immune response leading to life-threatening condition known as cytokine release syndrome, or autoimmune hemolytic anemia, immune thrombocytopenic purpura, Guillain-Barre syndrome, and the detection of different autoantibodies. This Research Topic includes seventeen contributions, fifteen original articles and two review articles, providing several new insights into the efficacy and safety of SARS-CoV-2 vaccine in autoimmune patients, immunologic biomarkers for diagnosis and therapeutic outcome of autoimmune arthritis

CO2 Concentration in Day Care Centres is Related to Wheezing in Attending Children

Poor ventilation at day care centres (DCCs) was already reported, although its effects on attending children are not clear. This study aimed to evaluate the association between wheezing in children and indoor CO2 (a ventilation surrogate marker) in DCC and to identify behaviours and building characteristics potentially related to CO2. In phase I, 45 DCCs from Lisbon and Oporto (Portugal) were selected through a proportional stratified random sampling. In phase II, 3 months later, 19 DCCs were further reassessed after cluster analysis for the greatest difference comparison. In both phases, children’s respiratory health was assessed by ISAAC-derived questionnaires. Indoor CO2 concentrations and building characteristics of the DCC were evaluated in both phases, using complementary methods. Mixed effect models were used to analyze the data. In phase I, which included 3,186 children (mean age 3.1±1.5 years), indoor CO2 concentration in the DCC rooms was associated with reported wheezing in the past 12months (27.5 %) (adjusted odds ratio (OR) for each increase of 200 ppm 1.04, 95 % CI 1:01 to 1:07). In phase II, the association in the subsample of 1,196 children seen in 19 out of the initial 45 DCCs was not significant (adjusted OR 1.02, 95 % CI 0.96 to 1.08). Indoor CO2 concentration was inversely associated with the practices of opening Windows and internal doors and with higher wind velocity. A positive trend was observed between CO2 and prevalence of reported asthma (4.7 %). Conclusion: Improved ventilation is needed to achieve a healthier indoor environment in DCC

Effect of indoor air quality of day care centers in children with different predisposition for asthma

BACKGROUND:Scarce information is available about the relationships between indoor air quality (IAQ) at day care centers (DCC), the estimated predisposition for asthma, and the actual wheezing susceptibility. METHODS:In the Phase II of ENVIRH study, 19 DCC were recruited after cluster analysis. Children were evaluated firstly using the ISAAC questionnaire and later by a follow-up questionnaire about recent wheezing. A positive asthma predictive index (API) was considered as predisposition for asthma. Every DCC was audited for IAQ and monitored for chemical and biologic contaminants. RESULTS:We included 1191 children, with a median age of 43 (P25 -P75 : 25-58) months. Considering the overall sample, in the first questionnaire, associations were found between CO2 concentration (increments of 200 ppm) and diagnosis of asthma (OR: 1.10; 95% CI: 1.00-1.20). Each increment of 100 μg/m(3) of total volatile organic compounds (TVOC) and 1 μg of Der p1/g of dust were associated with wheezing in the previous 12 months (OR: 1.06; 95% CI: 1.01-1.11 and OR: 1.06; 95% CI: 0.99-1.12, respectively). In the follow-up questionnaire, TVOC were again associated with wheezing (OR: 1.05; 95% CI: 1.00-1.11). Children exposed to fungal concentration above the 75th percentile had also higher odds of wheezing at follow-up. TVOC were associated with wheezing in children with either negative or positive API. CONCLUSIONS:IAQ in DCC seems to be associated with wheezing, in children with and without predisposition for asthma

Acculturation and use of health care services by Turkish and Moroccan migrants: a cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>There is insufficient empirical evidence which shows if and how there is an interrelation between acculturation and health care utilisation. The present study seeks to establish this evidence within first generation Turkish and Moroccan migrants, two of the largest migrant groups in present-day Western Europe.</p> <p>Methods</p> <p>Data were derived from the Amsterdam Health Monitor 2004, and were complete for 358 Turkish and 288 Moroccan foreign-born migrants. Use of health services (general practitioner, outpatient specialist and health care for mental health problems) was measured by means of self-report. Acculturation was measured by a structured questionnaire grading (i) ethnic self-identification, (ii) social interaction with ethnic Dutch, (iii) communication in Dutch within one's private social network, (iv) emancipation, and (v) cultural orientation towards the public domain.</p> <p>Results</p> <p>Acculturation was hardly associated with the use of general practitioner care. However, in case of higher adaptation to the host culture there was less uptake of outpatient specialist care among Turkish respondents (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.82-0.99) and Moroccan male respondents (OR = 0.81, 95% CI = 0.71-0.93). Conversely, there was a higher uptake of mental health care among Turkish men (OR = 0.81, 95% CI = 0.71-0.93) and women (OR = 0.81, 95% CI = 0.71-0.93). Uptake of mental health care among Moroccan respondents again appeared lower (OR = 0.74, 95% CI = 0.55-0.99). Language ability appeared to play a central role in the uptake of health care.</p> <p>Conclusion</p> <p>Some results were in accordance with the popular view that an increased participation in the host society is concomitant to an increased use of health services. However, there was heterogeneity across ethnic and gender groups, and across the domains of acculturation. Language ability appeared to play a central role. Further research needs to explore this heterogeneity into more detail. Also, other cultural and/or contextual aspects that influence the use of health services require further identification.</p

Interleukin-10 Mediated Autoregulation of Murine B-1 B-Cells and Its Role in Borrelia hermsii Infection

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. IL-10 inhibits TLR induced B-1P cell activation by blocking the classical NF-κB pathway. Co-stimulation with CD40 or BAFF abrogated the IL-10 inhibitory effect on B-1P cells during TLR stimulation. Finally, B-1P cells adoptively transferred from the peritoneal cavity of IL-10−/− mice showed better clearance of Borrelia hermsii than wild-type B-1P cells. This study described a novel autoregulatory property of B-1P cells mediated by B-1P cell derived IL-10, which may affect the function of B-1P cells in infection and autoimmunity

Measuring kinetic drivers of pneumolysin pore structure

Most membrane attack complex-perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins are thought to form pores in target membranes by assembling into pre-pore oligomers before undergoing a pre-pore to pore transition. Assembly during pore formation is into both full rings of subunits and incomplete rings (arcs). The balance between arcs and full rings is determined by a mechanism dependent on protein concentration in which arc pores arise due to kinetic trapping of the pre-pore forms by the depletion of free protein subunits during oligomerisation. Here we describe the use of a kinetic assay to study pore formation in red blood cells by the MACPF/CDC pneumolysin from Streptococcus pneumoniae. We show that cell lysis displays two kinds of dependence on protein concentration. At lower concentrations it is dependent on the pre-pore topore transition of arc oligomers, which we show to be a cooperative process. At higher concentrations it is dependent on the amount of pneumolysin bound to the membrane and reflects the affinity of the protein for its receptor, cholesterol. A lag occurs before cell lysis begins; this is dependent on oligomerisation of pneumolysin. Kinetic dissection of cell lysis by pneumolysin demonstrates the capacity of MACPF/CDCs to generate pore-forming oligomericstructures of variable size with, most likely, different functional roles in biology

What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea.</p> <p>Methods</p> <p>EMBASE^®, MEDLINE ^®and CINAHL^®databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes.</p> <p>Results</p> <p>We found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity.</p> <p>Conclusions</p> <p>Demonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.</p